| BackgroundWith the incidence of cancer increasing year by year,the number of patients who need chemotherapy is increasing gradually.According to statistics,about 20%-40%of cancer patients undergoing chemotherapy present chemotherapy induced peripheral neuropathy(CIPN),and it occurs primarily in patients received chemotherapy drugs such as paclitaxel,platinum,vincristine et al.CIPN is a dose-limited side effect,often with hyperalgesia or allodynia as the main symptoms.A lot of patients presented the corresponding symptoms in the process of chemotherapy or just ended,and even the first use.CIPN limits the dose of chemotherapy drugs and the duration of chemotherapy,and may lead to a reduction in the effectiveness of chemotherapy,thereby increasing mortality of cancer patients.The symptom of CIPN in some patients remains for months or even years after chemotherapy,reducing the quality of life in survivor greatly.There is no effective prevention and treatment for CIPN owing to the diversity of the action mechanisms of drugs.Platinum compounds are the first-line drugs for the treatment of colorectal cancer,and it mainly act on the nucleus DNA and create the Pt-DNA compounds,leading to apoptosis of tumor cells.Commonly used drugs include cisplatin,carboplatin,oxaliplatin,and lobaplatin.Lobaplatin is the third generation platinum chemotherapy drugs with higher stability,wider antitumor spectrum,stronger anti-tumor activity,lower toxicity and no cross resistance compared with other platinum,has been widely used in gastrointestinal cancer chemotherapy.In recent years,the incidence of rectal cancer in China has increased by 3.9%per year,far higher than the average level of 2%in the world.Surgery is the most fundamental and essential method in the treatment of rectal cancer.With the continuous improvement of medical care and the increasing demand for quality of life and health of people in China,laparoscopic surgery has gradually replaced the traditional laparotomy,becoming the preferred method for radical resection of rectal cancer.Despite the small trauma and rapid recovery after laparoscopic surgery,the pain is still the main complain after laparoscopic surgery and reduce the quality of life in the patient.Poor control to postoperative pain is a high risk factor for acute pain translating to chronic pain.Intraperitoneal chemotherapy(IPC)is a region chemotherapy based on the theory of tumor metastasis and chemotherapy principle.It is highly selective,not only directly kill residual and exfoliated tumor cells after surgery but also prevent liver metastasis.The effectiveness of IPC has been demonstrated by clinical trials which can prolong survival in colorectal cancer patients with peritoneal metastasis.Animal experiments have confirmed that single intraperitoneal use of platinum chemotherapy drugs can induce mechanical hyperalgesia in rats.However,there is no report about the effect of IPC on postoperative pain sensitivity in cancer patients and corresponding intervention.Our previous observation showed that intraoperative IPC with lobaplatin may cause early hyperalgesia in patients undergoing laparoscopic colorectal cancer surgery.Therefore,the following studies have been designed.In the first part,a prospective,randomized,controlled,double-blind study was conducted to investigate the effect of IPC with lobaplatin on early hyperalgesia in patients undergoing elective laparoscopic radical resection of colorectal cancer.In the second part,a prospective,randomized,controlled,double-blind study was conducted to investigate the effect of tranversus abdominis plane(TAP)block combined with dexmedetomidine on the pain hyperalgesia evoked by IPC in patients undergoing elective laparoscopic transabdominal resection of rectal cancer,aiming at provide a new analgesia mode for patients with intraoperative IPC which be great clinical importance.PART I The Effect of Intraperitoneal Chemotherapy on Early Pain Sensitivity in Patients following Elective Laparoscopic Transabdominal Resection of Rectal CancerObjective:To observe the effect of intraoperative Intraperitoneal Chemotherapy(IPC)with lobaplatin on pain sensitivity in patients undergoing elective laparoscopic transabdominal resection of rectal cancer.Methods:Eighty patients undergoing laparoscopic transabdominal radical resection of rectal cancer were assigned to the control group(Group C,treated by normal saline)and lobaplatin group(Group L,treated with lobaplatin)in this double-blind,randomized study.All patients received PCA postoperativel,and all the patients in the two groups were treated with the same systemic chemotherapy.The PCIA formula was 0.8%sufentanil in 300 mL.The primary outcome measure was consumption of sufentanil at 4 h,24 h,48 h,and 72 h after surgery while the secondary outcome measures were baseline characteristics,requirement of drugs during the operation,pain intensity(numerical rating scale,NRS),functional activity score(FAS),rescue analgesic requirement,and the side effect of nausea and vomiting,itching,severe respiratory depression and dizziness during 72 h after the surgeryResults:All the two groups were similar in terms of patient characteristics.Compared with the Group C,the cumulative dose of sufentanil at 4 h,24 h,48 h,and 72 h after surgery in Group L increased significantly(P<0.05).The NRS scores of the two groups were lower and compared with Group C,the patients in Group L had significantly higher NRS at rest at 4 h,24 h,48 h and 72 h,and significantly higher NRS with coughing at 24 h,48 h and 72 h after surgery(P<0.05).Compared with Group C,the FAS classification of the patients in the Group L decreased significantly at 4 h,24 h after surgery(P<0.05),but the difference of the FAS classification at 48 h,and 72 h after surgery between the two groups were not different statistically.There was no statistical difference in the use of rescue analgesics between the two groups.There was no statistical difference in the incidence of side effect between the two groups during 72 h after surgery.No patient present severe respiratory depression postoperatively.Conclusion:The IPC with lobaplatin in patients following elective laparoscopic transabdominal radical resection of rectal cancer can significantly increase consumption of sufentanil,pain intensity.This founding is particularly important for the postoperative analgesia in patients with intraoperative IPC.PART ? The Effect of Tranversus Abdominis Plane Block combined with Dexmedetomidine on the Pain Hyperalgesia Evoked by Chemotherapy in Patients undergoing Elective Laparoscopic Transabdominal Resection of Rectal Cancer Objective:To observe the effect of postoperative tranversus abdominis plane(TAP)block combined with intraoperative infusion of dexmedetomidine on the reqirement of analgesics and the pain intensity during 72 hours after surgery in patients following laparoscopic radical resection of colorectal cancer.Method:Ninety patients undergoing laparoscopic transabdominal radical resection of rectal cancer were assigned to the control group(Group C,treated by normal saline),dexmedetomidine group(Group D,treated with intraoperative dexmedetomidine infusion at 0.1 mL/kg/h)and TAP group(Group T,treated with intraoperative dexmedetomidine infusion at 0.1 mL/kg/h combined with postoperative TAP block)in this double-blind,randomized study.All patients received PCA postoperatively.The PCIA formula was 0.8%sufentanil in 300 mL.The primary outcome:measure was consumption of sufentanil during 0-24 h,24-48 h,and 48-72 h after surgery while the secondary outcome measures were baseline characteristics,requirement of drugs during the operation,pain intensity(numerical rating scale,NRS),functional activity score(FAS),rescue analgesic requirement,and the side effect of nausea and vomiting,itching,severe respiratory depression and dizziness during 72 h after the surgery.Results:All the three groups were similar in terms of patient characteristics.Compared with the Group C,the cumulative dose of sufentanil during 0-24 h,24-48 h,and 48-72 h after surgery in Group T decreased significantly(P<0.05).Compared with the Group D,the cumulative dose of sufentanil during 0-24 h,24-48 h,and 48-72 h after surgery in Group T decreased significantly(P<0.05).There were no statistically significant differences between the Group D and Group C in terms of consumption of sufentanil during 0-24 h,24-48 h,and 48-72 h after surgery.The NRS scores of the three groups were lower.There were no statistically significant differences among the three groups in terms of NRS scores when at rest and while coughing at 24 h,48 h,72 h after surgery.Compared with the Group C and Group D,the requirement of rescue analgesia was significantly lower in Group T(P<0.05).There was no statistical difference in the incidence of side effect among the three groups during the 72 h after surgery.No patient present severe respiratory depression postoperatively.Conclusion:The intraoperative dexmedetomidine infusion(0.4 ?g/kg/h)combined with ultrasound-guided TAP block can reduce the opioid consumption and provide perfect analgesia in patients following laparoscopic transabdominal resection of rectal cancer.This study provides a new analgesic strategy for postoperative pain with intraperitoneal chemotherapy following laparoscopic transabdominal resection of rectal cancer. |
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